Acetyl-CoA Carboxylase α Is Essential to Breast Cancer Cell Survival
Open accessAbstract
Activation of de novo fatty acid synthesis is a characteristic feature of cancer cells. We have recently described an interaction between acetyl-CoA carboxylase α (ACCα), a key enzyme in fatty acid synthesis, and BRCA1, which indicates a possible connection between lipid synthesis and genetic factors involved in susceptibility to breast and ovarian cancers. For this reason, we explored the role of ACCα in breast cancer cell survival using an RNA interference (RNAi) approach. We show that specific silencing of either the ACCα or the fatty acid synthase (FAS) genes in cancer cells results in a major decrease in palmitic acid synthesis. Depletion of the cellular pool of palmitic acid is associated with induction of apoptosis concomitant with the formation of reactive oxygen species (ROS) and mitochondrial impairment. Expression of a small interfering RNA (siRNA)–resistant form of ACCα mRNA prevented the effect of ACCα-RNAi but failed to prevent the effect of FAS gene silencing. Furthermore, supplementation of the culture medium with palmitate or with the antioxidant vitamin E resulted in the complete rescue of cells from both ACCα and FAS siRNA–induced apoptosis. Finally, human mammary epithelial cells are resistant to RNAi against either ACCα or FAS. These data confirm the importance of lipogenesis in cancer cell survival and indicate that this pathway represents a key target for antineoplastic therapy that, however, might require specific dietary recommendation for full efficacy. (Cancer Res 2006; 66(10): 5287-94)
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Genetic knockdown of ACC induces apoptosis in cancer cell lines.
“Genetic knockdown of ACC induces apoptosis in cancer cell lines (Brusselmans et al., 2005; Chajes et al., 2006), and an allosteric inhibitor of ACC, ND-646, has shown antitumor efficacy in autochthonous mouse lung tumor models (Svensson et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Chajes et al., 2006
ACLY, ACC, and FASN are frequently upregulated in transformed cells, and their inhibition reduces tumor cell growth in vitro and in vivo.
“In fact, all three major components involved in fatty acyl chain biosynthesis – ACLY, ACC and FASN – are frequently upregulated in transformed cells; furthermore, their inhibition reduces tumor cell growth in vitro and in vivo (Chajes et al., 2006; Flavin et al., 2010; Migita et al., 2008; Milgraum et al., 1997).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Chajes et al., 2006
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- Authors
- Chajès, V., Cambot, M., Moreau, K., Lenoir, G. M., & Joulin, V.
- Affiliations
- 1Centre National de la Recherche Scientifique-FRE 2939, Institut Gustave Roussy, Villejuif, France and
- Centre National de la Recherche Scientifique (FR)
- Venue
- Cancer Research
- Published
- 2006-05-15
- Volume
- 66
- Issue
- 10
- Pages
- 5287-5294
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2140625991
- Cited by
- 347
- References
- 34
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 19 · 2023: 15 · 2022: 16 · 2021: 30 · 2020: 27 · 2019: 17 · 2018: 22 · 2017: 17 · 2016: 17 · 2015: 22 · 2014: 19 · 2013: 14 · 2012: 18
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- ACACA, fatty acid synthase, de novo lipogenesis, lipogenesis, palmitic acid, apoptosis, reactive oxygen species, mitochondrial dysfunction, BRCA1, vitamin E, mammary epithelial cells
- MeSH terms
- Acetyl-CoA Carboxylase, Breast Neoplasms, Fatty Acids, Humans, RNA, Messenger, Apoptosis, Palmitic Acid, Gene Silencing, RNA, Small Interfering, Cell Line, Tumor, Cell Growth Processes, Lipogenesis, Fatty Acid Synthases
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